The prevention and control of inflammation is often of great importance for the treatment of humans and animals. Much research has been devoted to development of compounds having anti-inflammatory properties. Certain methods and chemical compositions have been developed which aid in inhibiting or controlling inflammation, but additional anti-inflammatory methods and compositions are needed.
It has been found that some natural products and organisms are potential sources for chemical molecules having useful biological activity of great diversity. Marine sponges have proved to be such a source, and a number of publications have issued disclosing organic compounds derived from marine sponges. Such publications include Scheuer, P. J. Ed. (1978-1983) Marine Natural Products, Chemical and Biological Perspectives, Academic Press, New York; Faulkner, D. (1995) J. Nat. Prod. Rep. 12:223-269; (1994) 11:355-394; (1993) 10:497-539; (1992) 9:323-364; (1991) 8:97-147; (1990) 7:269-309; (1988) 5:613-663; (1987) 4:539-576; (1986) 3:1-33; (1984) 1:551-598.
Indole compounds of marine origin have also been described in Moquin, C., M. Guyot (1984) Tetrahedron Letters 25 (44):5047-5048; Norton, R. S., R. J. Wells (1982) J. Am. Chem. Soc. 104: 3628-3635; Roll, D. M., C. M. Iireland, H. S. M. Lu, J. Clardy (1988) J. Org. Chem, 53:3276; Kobayashi, H., T. Ohta, S. Nozoe (1990) Tetrahedron 46:7699; Jiminez C., E. Quinoa, P. Crews, (1991) Tetrahedron Lett. 32:1843; Jiminez, C., E. QUinoa, M. Adamczeski, L. M. Hunter, P. Crews (1991) J. Org. Chem. 56:3403; Bifulco, G., I. Bruno, L. .Minale, R. Riccio, A. Calignano, C. Debitus (1994) J. Nat. Prod. 57:1294; and Bifulco, G., I. Bruno, R. Riccio, J. Lavayre, G. Bourdy (1995) J. Nat. Prod. 58:1254.
Utilizing sponges as a source material and supplemented by synthetic production methods, new classes of biologically active compounds and new pharmaceutical compositions useful as antitumor and antiviral agents have been provided to the art. For example, bis-heterocyclic compounds such as bis-indoles have been previously described as having antimicrobial, antitumoror antiviral activity. Specifically, the bis-indole compounds known as topsentins are disclosed in U.S. Pat. No. 4,866,084. Dragmacidin and its related compounds isolated from the marine sponge of the Dragmacidon sp. are disclosed in U.S. Pat. No.4,895,844. These patents are herein incorporated by reference. These compounds as well as the homocarbonyltopsentins and hamacanthins have also been described as having inhibitory activity against cellular inflammatory responses. See U.S. Pat. Nos. 5,290,777 and 5,464,835, which are also hereby incorporated by reference. The present invention provides additional related compounds which have improved water solubility characteristics and which have a novel utility as anti-neurogenic inflammatory compositions.
Other advantages and further scope of applicability of the present invention will become apparent from the detailed descriptions given herein; it should be understood, however, that the detailed descriptions, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent from such descriptions.